title: Physico-chemical stability of eribulin mesylate containing concentrate and ready-to-administer solutions.
abstract: OBJECTIVE
  The aim of this study was to determine the stability of commercially available eribulin mesylate containing injection solution as well as diluted ready-to-administer solutions stored under refrigeration or at room temperature.
  
  
  METHODS
  Stability was studied by a novel developed stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay with ultraviolet detection (detection wavelength 200 nm). Triplicate test solutions of eribulin mesylate containing injection concentrate (0.5 mg/mL) and with 0.9% sodium chloride solution diluted ready-to-administer preparations (0.205 mg/mL eribulin mesylate in polypropylene (PP) syringes, 0.020 mg/mL eribulin mesylate in polypropylene/polyethylene (PE) bags) were stored protected from light either at room temperature (25) or under refrigeration (2-8). Samples were withdrawn on day 0 (initial), 1, 3, 5, 7, 14, 21 and 28 of storage and assayed. Physical stability was determined by measuring the pH value once a week and checking for visible precipitations or colour changes.
  
  
  RESULTS
  The stability tests revealed that concentrations of eribulin mesylate remained unchanged over a period of 28 days irrespective of concentration, container material or storage temperature. Neither colour changes nor visible particles have been observed. The pH value varied slightly over time but remained in the stability favourable range of 5-9.
  
  
  CONCLUSIONS
  Eribulin mesylate injection (0.5 mg/mL) is physico-chemically stable over a period of 28 days after first puncture of the vial. After dilution with 0.9% NaCl vehicle solution, ready-to-administer eribulin mesylate injection solutions (0.205 mg/mL in PP syringe) and infusion solutions (0.02 mg/mL in prefilled PP/PE bags) are physico-chemically stable for a period of at least four weeks either refrigerated or stored at room temperature. For microbiological reasons storage under refrigeration is recommended.
authors.affiliation: Department of Pharmacy, University Medical Center Mainz, Johannes Gutenberg-University, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Spindeldreier
authors.forename: Judith
authors.initials: J
authors.lastname: Thiesen
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Lipp
authors.forename: Irene
authors.initials: I
authors.lastname: Krämer
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004349:Drug Packaging; D004355:Drug Stability; D005663:Furans / Q000008:administration & dosage / Q000737:chemistry*; D007659:Ketones / Q000008:administration & dosage / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D015203:Reproducibility of Results; D000095662:Polyether Polyketides
chemical_list: D005663:Furans; D007659:Ketones; D019999:Pharmaceutical Solutions; C490954:eribulin; D000095662:Polyether Polyketides
keywords: Eribulin mesylate; high-performance liquid chromatography; physico-chemical stability